This project is an application to use genetic therapy directed against KS apoptotic mechanisms. Based on preliminary evidence found by this and other groups, the Bcl-2 and Bcl-xl gene products are expressed by KS cells in vivo and in vitro. The approach is to inactivate these gene products with a repressor, Bcl-xs. An adenovirus vector expressing Bcl-xs has been constructed. Thus far it has been lethal to all KS cells examined, presumably by induction of apoptosis. The hypothesis is that this or a similar virus vector may be a useful novel therapeutic agent for KS treatment. The specific aims are to: (1) determine the molecular mechanism by which the Bcl-xs adenovirus kills KS cells; (2) to determine whether expression of Bcl-2, Bcl-xl or the HIV tat gene product in KS cells affect the efficiency of killing by the bcl-xs adenovirus vector; (3) to determine the effect of the bcl-xs adenovirus on a spectrum of normal cells and KS cells; and (4) to assess the possible in vivo therapeutic utility of the bcl-xs adenovirus in an animal model of KS.